Biology subjects

Kuhl, H.

Publications and source records attributed to Kuhl, H..

7 recordsLinked to original sources

bioRxiv2024

Convergent and lineage-specific genomic changes contribute to adaptations in sugar-consuming birds

High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummingbirds, parrots, honeyeaters, and sunbirds by generating nine new genomes and 90 tissue-specific transcriptomes. Comparative screens revealed an excess of repeated selection in both protein-coding and regulatory sequences in sugar-feeding birds, suggesting reuse of genetic elements. Sequence or expression changes in sugar-feeders affect genes involved in blood pressure regulation, lipid, amino acid and carbohydrate metabolism, with experiments showing functional changes in honeyeater hexokinase 3. MLXIPL, a key regulator of sugar and lipid homeostasis, showed convergent sequence and regulatory changes across all sugar-feeding clades; experiments revealed enhanced sugar-induced transcriptional activity of hummingbird MLXIPL, highlighting its adaptive role in high-sugar diets. Summary Figure: Our comparative screens across four independent sugar-feeding bird groups identified both repeated and lineage-specific targets of selection O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=65 SRC="FIGDIR/small/610474v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@148f5c8org.highwire.dtl.DTLVardef@1005dbaorg.highwire.dtl.DTLVardef@1097facorg.highwire.dtl.DTLVardef@9d365c_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2024

The haplotype-resolved Prymnesium parvum (type B) microalga genome reveals the genetic basis of its fish-killing toxins

The catastrophic loss of aquatic life in the Central European Oder River in 2022, caused by a toxic bloom of the haptophyte microalga Prymnesium parvum (in a wide sense, s.l.), underscores the need to improve our understanding of the genomic basis of the toxin. Previous morphological, phylogenetic, and genomic studies have revealed cryptic diversity within P. parvum s.l. and uncovered three clade-specific (types A, B, C) prymnesin toxins. Here, we used state-of-the-art long-read sequencing and assembled the first haplotype-resolved diploid genome of a P. parvum type B, the strain responsible for the Oder disaster. Comparative analyses with type A genomes uncovered a genome-size expansion driven by repetitive elements in type B. We also found conserved chromosomal synteny but divergent evolution in several polyketide synthase (PKS) genes, which are known to underlie toxin production in combination with environmental cues. We identified a specific, approximately 20 kilobase pair comprising deletion in the largest PKS gene of type B that we link to differences of the chemical structure of types A and B prymnesins. Electron-microscopy and flow cytometry confirmed diploidy in the Oder River strain and differences to closely related strains in morphology and ploidy. Our results provide unprecedented resolution of strain diversity in P. parvum and a better understanding of the genomic basis of toxin variability in haptophytes. The reference-quality genome will help to understand changes to microbial diversity in the face of increasing environmental pressures, and provides a basis for strain-level monitoring of invasive Prymnesium in the future.

genomics↗

bioRxiv2023

Multi-genome comparisons reveal gain-and-loss evolution of the anti-Mullerian hormone receptor type 2 gene, an old master sex determining gene, in Percidae

The Percidae family comprises many fish species of major importance for aquaculture and fisheries. Based on three new chromosome-scale assemblies in Perca fluviatilis, Perca schrenkii and Sander vitreus along with additional percid fish reference genomes, we provide an evolutionary and comparative genomic analysis of their sex-determination systems. We explored the fate of a duplicated anti-Mullerian hormone receptor type-2 gene (amhr2bY), previously suggested to be the master sex determining (MSD) gene in P. flavescens. Phylogenetically related and structurally similar amhr2 duplications (amhr2b) were found in P. schrenkii and Sander lucioperca, potentially dating this duplication event to their last common ancestor around 19-27 Mya. In P. fluviatilis and S. vitreus, this amhr2b duplicate has been lost while it was subject to amplification in S. lucioperca. Analyses of the amhr2b locus in P. schrenkii suggest that this duplication could be also male-specific as it is in P. flavescens. In P. fluviatilis, a relatively small (100 kb) non-recombinant sex-determining region (SDR) was characterized on chromosome-18 using population-genomics approaches. This SDR is characterized by many male-specific single-nucleotide variants (SNVs) and no large duplication/insertion event, suggesting that P. fluviatilis has a male heterogametic sex determination system (XX/XY), generated by allelic diversification. This SDR contains six annotated genes, including three (c18h1orf198, hsdl1, tbc1d32) with higher expression in testis than ovary. Together, our results provide a new example of the highly dynamic sex chromosome turnover in teleosts and provide new genomic resources for Percidae, including sex-genotyping tools for all three known Perca species.

genomics↗

bioRxiv2023

A novel amphibian sex determination candidate gene, evolved by structural variation in the regulatory region between X and Y

Most vertebrates develop distinct females and males, where sex is determined by repeatedly-evolved environmental or genetic triggers. Undifferentiated sex chromosomes and large genomes have caused major knowledge gaps in amphibians. Only a single master sex-determining gene is known in >8650 species, the dmrt1-paralogue (dm-w) of female-heterogametic clawed frogs (Xenopus; ZW[female]/ZZ[male]). Combining chromosome-scale female and male genomes of a non- model amphibian, the European green toad, Bufo(tes) viridis, with ddRAD- and whole genome pool-sequencing revealed a candidate master locus, governing a male-heterogametic system (XX[female]/XY[male]). Targeted sequencing across multiple taxa uncovered structural X/Y-variation in the 5-regulatory region of the gene bod1l, where a Y-specific non-coding RNA, only expressed in males, suggests that this locus may initiate sex-specific differentiation. Developmental transcriptomes and RNA in-situ hybridization show timely and spatially relevant, sex-specific ncRNA-Y and bod1l-gene expression in primordial gonads with coinciding differential H3K4me- methylation in pre-granulosa/pre-Sertoli cells, pointing to a specific mechanism of amphibian sex determination.

genomics↗

bioRxiv2020

A 180 My-old female-specific genome region in sturgeon reveals the oldest known vertebrate sex determining system with undifferentiated sex chromosomes

Several hypotheses explain the prevalence of undifferentiated sex chromosomes in poikilothermic vertebrates. Turnovers change the master sex determination gene, the sex chromosome or the sex determination system (e.g. XY to WZ). Jumping master genes stay main triggers but translocate to other chromosomes. Occasional recombination (e.g. in sex-reversed females) prevents sex chromosome degeneration. Recent research has uncovered conserved heteromorphic or even homomorphic sex chromosomes in several clades of non-avian and non-mammalian vertebrates. Sex determination in sturgeons (Acipenseridae) has been a long-standing basic biological question, linked to economical demands by the caviar-producing aquaculture. Here, we report the discovery of a sex-specific sequence from sterlet (Acipenser ruthenus). Using chromosome-scale assemblies and pool-sequencing, we first identified a ~16 kb female-specific region. We developed a PCR-genotyping test, yielding female-specific products in six species, spanning the entire phylogeny with the most divergent extant lineages (A. sturio, A. oxyrinchus vs. A. ruthenus, Huso huso), stemming from an ancient tetraploidization. Similar results were obtained in two octoploid species (A. gueldenstaedtii, A. baerii). Conservation of a female-specific sequence for a long period, representing 180 My of sturgeon evolution, and across at least one polyploidization event, raises many interesting biological questions. We discuss a conserved undifferentiated sex chromosome system with a ZZ/ZW-mode of sex determination and potential alternatives.

evolutionary biology↗

bioRxiv2019

Crowdfunded whole-genome sequencing of the celebrity cat Lil BUB identifies causal mutations for her osteopetrosis and polydactyly

Rare diseases and their underlying molecular causes are often poorly studied, posing challenges for patient diagnosis and prognosis. The development of next-generation sequencing and its decreasing costs promises to alleviate such issues by supplying personal genomic information at a moderate price. Here, we used crowdfunding as an alternative funding source to sequence the genome of Lil BUB, a celebrity cat affected by rare disease phenotypes characterized by supernumerary digits, osteopetrosis and dwarfism, all phenotypic traits that also occur in human patients. We discovered that Lil BUB is affected by two distinct mutations: a heterozygous mutation in the limb enhancer of the Sonic hedgehog gene, previously associated with polydactyly in Hemingway cats; and a novel homozygous frameshift deletion affecting the TNFRSF11A (RANK) gene, which has been linked to osteopetrosis in humans. We communicated the progress of this project to a large online audience, detailing the inner workings of personalized whole genome sequencing with the aim of improving genetic literacy. Our results highlight the importance of genomic analysis in the identification of disease-causing mutations and support crowdfunding as a means to fund low-budget projects and as a platform for scientific communication.

genetics↗

bioRxiv2017

Wild tobacco genomes reveal the evolution of nicotine biosynthesis

Nicotine, the signature alkaloid of Nicotiana species responsible for the addictive properties of human tobacco smoking, functions as a defensive neurotoxin against attacking herbivores. However, the evolution of the genetic features that contributed to the assembly of the nicotine biosynthetic pathway remains unknown. We sequenced and assembled genomes of two wild tobaccos, Nicotiana attenuata (2.5 Gb) and N. obtusifolia (1.5 Gb), two ecological models for investigating adaptive traits in nature. We show that after the Solanaceae whole genome triplication event, a repertoire of rapidly expanding transposable elements (TEs) bloated these Nicotiana genomes, promoted expression divergences among duplicated genes and contributed to the evolution of herbivory-induced signaling and defenses, including nicotine biosynthesis. The biosynthetic machinery that allows for nicotine synthesis in the roots evolved from the stepwise duplications of two ancient primary metabolic pathways: the polyamine and nicotinic acid dinucleotide (NAD) pathways. While the duplication of the former is shared among several Solanaceous genera which produce polyamine-derived tropane alkaloids, the innovation and efficient production of nicotine in the genus Nicotiana required lineage-specific duplications within the NAD pathway and the evolution of root-specific expression of the duplicated Solanaceae-specific ethylene response factor (ERF) that activates the expression of all nicotine biosynthetic genes. Furthermore, TE insertions that incorporated transcription factor binding motifs also likely contributed to the coordinated metabolic flux of the nicotine biosynthetic pathway. Together, these results provide evidence that TEs and gene duplications facilitated the emergence of a key metabolic innovation relevant to plant fitness.

genomics↗